The dynamics and mechanisms of interleukin-1alpha and beta nuclear import.
Pro-inflammatory members of the interleukin-1 (IL-1) family of cytokines (IL-1alpha and beta) are important mediators of host defense responses to infection but can also exacerbate the damaging inflammation that contributes to major human diseases. IL-1alpha and beta are produced by cells of the innate immune system, such as macrophages, and act largely after their secretion by binding to the type I IL-1 receptor on responsive cells. There is evidence that IL-1alpha is also a nuclear protein that can act intracellularly. In this study, we report that both IL-1alpha and IL-1beta produced by microglia (central nervous system macrophages) in response to an inflammatory challenge are distributed between the cytosol and the nucleus. Using IL-1-beta-galactosidase and IL-1-green fluorescent protein chimeras (analyzed by fluorescence recovery after photobleaching), we demonstrate that nuclear import of IL-1alpha is exclusively active, requiring a nuclear localization sequence and Ran, while IL-1beta nuclear import is entirely passive. These data provide valuable insights into the dynamic regulation of intracellular cytokine trafficking.
Luheshi
Nadia M
NM
Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester, UK.
Rothwell
Nancy J
NJ
Brough
David
D
D021581:Active Transport, Cell Nucleus; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D053582:Interleukin-1alpha / Q000235:genetics / Q000378:metabolism*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D017628:Microglia / Q000378:metabolism; D008969:Molecular Sequence Data; D019913:Nuclear Localization Signals; D011499:Protein Processing, Post-Translational; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D019913:Nuclear Localization Signals; D011994:Recombinant Proteins